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. 2013 Jun 17:9:1164-9.
doi: 10.3762/bjoc.9.130. Print 2013.

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

Loránd Kiss  1 , Melinda Nonn, Reijo Sillanpää, Santos Fustero, Ferenc Fülöp
Affiliations

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

Loránd Kiss et al. Beilstein J Org Chem. .

Abstract

A regio- and stereoselective method has been developed for the synthesis of novel fluorinated 2-aminocyclohexanecarboxylic acid derivatives with the fluorine attached to position 4 of the ring. The synthesis starts from either cis- or trans-β-aminocyclohex-4-enecarboxylic acids and involves regio- and stereoselective transformation of the ring C-C double bond through iodooxazine formation and hydroxylation, followed by hydroxy-fluorine or oxo-fluorine exchange.

Keywords: amino acids; epoxidation; fluorination; hydroxylation; stereoselective reaction.

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Figures

Scheme 1
Scheme 1
Synthesis of all-cis ethyl 4-hydroxylated β-aminocyclohexanecarboxylate 5.
Figure 1
Figure 1
ORTEP diagram of iodooxazinone 2. Thermal ellipsoids have been drawn at the 20 % probability level.
Figure 2
Figure 2
ORTEP diagram of hydroxylated amino ester 5. Thermal ellipsoids have been drawn at the 20% probability level.
Scheme 2
Scheme 2
Syntheses of fluorinated amino esters 7 and 9.
Scheme 3
Scheme 3
Synthesis of ethyl 4-hydroxy-β-aminocyclohexanecarboxylate 14.
Figure 3
Figure 3
ORTEP diagram of iodooxazinone derivative 12. Thermal ellipsoids have been drawn at the 20% probability level.
Figure 4
Figure 4
ORTEP diagram of hydroxylated amino ester 14. The water molecule oxygen atom O4 is situated on the twofold axis with a population parameter of 0.6. Thermal ellipsoids have been drawn at the 20% probability level.
Scheme 4
Scheme 4
Syntheses of fluorinated amino esters 16 and 18.
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